1. Field of the Invention
The present invention relates generally to the fields of immunology and protein chemistry. More specifically, the present invention relates to the use of curcumin to inhibit activation of the transcription factor, NF.kappa.B
2. Description of the Related Art
Members of the transcription factor NF-.kappa.B family play a central role in various responses leading to host defense, activating a rapid progression of gene expression. These transcription factors are dimeric complexes composed of different members of the Rel/NF-.kappa.B family of polypeptides. This family is distinguished by the presence of a Rel homology domain of about 300 amino acids that displays a 35% to 61% identity between various family members (for references see 1). Although NF-.kappa.B is a ubiquitous transcription factor, it plays a critical role in the cells of the immune system, where it controls the expression of various cytokines and the major histocompatibility complex genes. The inappropriate regulation of NF-.kappa.B and its dependent genes have been associated with various pathological conditions including toxic/septic shock, graft vs host reaction, radiation damage, atherosclerosis, and cancer (1, 2). Thus, NF-.kappa.B is an important target for therapeutic intervention.
Unlike other transcription factors, the NF-.kappa.B proteins and other members of the Rel family reside in the cytoplasm in a n inactive state but upon activation, they are translocated to the nucleus. The nuclear translocation of Rel proteins is induced b y many agents, including inflammatory cytokines (e.g., tumor necrosis factor (TNF), lymphotoxin (LT), and interleukin (IL)-1), mitogens, bacterial products, protein synthesis inhibitors, oxidative stress (H.sub.2 O.sub.2), ultraviolet light, and phorbol esters (3, 4). Upon activation of NF-.kappa.B, a large number of genes are induced including various inflammatory cytokines, adhesion molecules, and Rel proteins (for reviews 3 and 4).
Curcumin (diferuloylmethane) has been shown to block many reactions in which NF-.kappa.B plays a major role. This agent is a major active component of turmeric (Curcuma longa) and gives specific flavor and yellow color to curry. The compound has been shown to display anticarcinogenic properties in animals as indicated by its ability to inhibit both tumor initiation induced by benz (a) pyrene and 7,12 dimethylbenz (a) anthracene (5-8) and tumor promotion induced by phorbol esters (9,10), which are known to activate NF-.kappa.B. Curcumin has also been shown to inhibit type 1 human immunodeficiency virus long terminal repeat (HIV-LTR) directed gene expression and virus replication stimulated by TNF and phorbol ester (11), which likewise require NF-.kappa.B activation. The anti-inflammatory and antioxidant properties of curcumin have been well documented (12-14). How these inhibitory responses are modulated by curcumin is not understood.
The prior art is deficient in the lack of effective means of inhibiting the activation of the transcription factor, NF.kappa.B. The present invention fulfills this longstanding need and desire in the art.